<p>Despite the excellent efficacy of carbapenems against a broad spectrum of bacteria, their clinical application is limited to multiple daily injections due to poor oral bioavailability and rapid pH-dependent hydrolysis. Liposomal nanocarriers protect encapsulated therapeutics from degradation, facilitate controlled release, and reduce both dosing frequency and systemic toxicity. Conventional liposomes, however, face stability issues, premature drug leakage, and opsonization, leading to short circulation times. Silk fibroin (SF) coating improves nanocarrier stability, prevents aggregation and drug leakage, and reduces opsonization to extend circulation. In this study, SF-coated, meropenem-loaded liposomes (MPL@SF) were prepared and evaluated for their physicochemical and biological properties. The optimized system showed a mean size of 267 ± 8&#xa0;nm with a PDI of 0.20 ± 0.04, encapsulation efficiency of 94.0 ± 3.9%, and loading content of 31.0 ± 2.5%. The nanosystem exhibited sustained release, with 92.0 ± 7% of meropenem released after 36&#xa0;h. Molecular dynamics simulations confirmed enhanced lateral lipid diffusion without structural disruption of the bilayer. Collectively, these findings demonstrate that silk fibroin-coated liposomes (L@SF) represent a promising strategy to address the administration challenges associated with meropenem.</p> Graphical Abstract <p></p>

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Silk Fibroin Modulated Meropenem Delivery and Enhanced Antibacterial Activity: An Integrated Experimental and Computational Study

  • Shokoufeh Rahmani,
  • Ghazal Nowroozi,
  • Mohsen Shahlaei,
  • Hadi Hossainpour,
  • Zahra Asvar,
  • Sajad Moradi

摘要

Despite the excellent efficacy of carbapenems against a broad spectrum of bacteria, their clinical application is limited to multiple daily injections due to poor oral bioavailability and rapid pH-dependent hydrolysis. Liposomal nanocarriers protect encapsulated therapeutics from degradation, facilitate controlled release, and reduce both dosing frequency and systemic toxicity. Conventional liposomes, however, face stability issues, premature drug leakage, and opsonization, leading to short circulation times. Silk fibroin (SF) coating improves nanocarrier stability, prevents aggregation and drug leakage, and reduces opsonization to extend circulation. In this study, SF-coated, meropenem-loaded liposomes (MPL@SF) were prepared and evaluated for their physicochemical and biological properties. The optimized system showed a mean size of 267 ± 8 nm with a PDI of 0.20 ± 0.04, encapsulation efficiency of 94.0 ± 3.9%, and loading content of 31.0 ± 2.5%. The nanosystem exhibited sustained release, with 92.0 ± 7% of meropenem released after 36 h. Molecular dynamics simulations confirmed enhanced lateral lipid diffusion without structural disruption of the bilayer. Collectively, these findings demonstrate that silk fibroin-coated liposomes (L@SF) represent a promising strategy to address the administration challenges associated with meropenem.

Graphical Abstract